An in vivo avian model of human melanoma to perform rapid and robust preclinical studies.

ABSTRACT: Metastatic melanoma patients carrying a BRAF^V600 mutation can be treated with a combination of BRAF and MEK inhibitors (BRAFi/MEKi), but innate and acquired resistance invariably occurs. Predicting patient response to targeted therapies is crucial to guide clinical decision. We describe here the development of a highly efficient patient-derived xenograft model adapted to patient melanoma biopsies, using the avian embryo as a host (AVI-PDX^TM ). In this in vivo paradigm, we depict a fast and reproducible tumor engraftment of patient samples within the embryonic skin, preserving key molecular and phenotypic features. We show that sensitivity and resistance to BRAFi/MEKi can be reliably modeled in these AVI-PDX^TM , as well as synergies with other drugs. We further provide proof-of-concept that the AVI-PDX^TM models the diversity of responses of melanoma patients to BRAFi/MEKi, within days, hence positioning it as a valuable tool for the design of personalized medicine assays and for the evaluation of novel combination strategies.

SUBMITTER: Jarrosson L 

PROVIDER: S-EPMC9994476 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature